Prevention of Early Mortality by Presumptive Tuberculosis (TB) Treatment

NCT ID: NCT01417988

Last Updated: 2014-02-17

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-08-31
• Study Completion Date: 2013-06-30

Brief Summary

This study investigates the prevention of early mortality in patients initiating antiretroviral therapy (ART) in sub-Saharan Africa where 79% of the co-infected cases of TB reside. Many published studies have shown a surprisingly high proportion of all patients initiated on ART dying within 6 months (8-26%) with increasing risk with decreasing CD4 T cell count. The majority (median 70%) occur in the first 3 months with the greatest proportion of deaths due to previously undiagnosed tuberculosis (TB). The investigators will enroll patients from 4 geographically diverse countries (Gabon, Mozambique, South Africa, and Uganda) in a randomized open label clinical trial targeting a population of people with high mortality risk; patients with CD4 T cell count < 50 cells/μl and body mass index (BMI) < 18 kg/m2. Severely immunocompromised patients with low BMI in the intervention arm will receive presumptive anti-TB 4-drug chemotherapy and subsequently initiate ART within 2 weeks compared to ART alone. The main objective is to measure and compare early mortality in the group presumptively treated for TB in addition to ART. Other sub-objectives are to determine the predictors of early mortality and the causes of death by autopsy (traditional and verbal), to determine if presumptive anti-TB treatment affects viral suppression with ART, and to assess incidence rates and characterize drug toxicity in patients dually treated. Because of the high rates of TB co-infection in sub-Saharan Africa in the HIV-infected, the investigators expect that patients presumptively treated for TB in addition to HIV will have a lower mortality rate than patients receiving ART only. This trial is expected to be of great public health benefit and generalisability.

Conditions

HIV Infection; Tuberculosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Empiric TB treatment

Empiric initiation of 4 drug TB treatment (8 weeks of 4 drug, 16 weeks of 2 drug therapy) followed by ART (efavirenz-based) within 2 weeks

Group Type: EXPERIMENTAL

Experimental: Empiric TB treatment

Intervention Type: DRUG

Initiation of 4 drug TB treatment (8 weeks of 4 drug, 16 weeks of 2 drug therapy) followed by ART (efavirenz-based) within 2 weeks

ART only arm

ART (efavirenz-based) only (+ pyridoxine 50mg) given within 2 weeks after enrolment

Group Type: ACTIVE_COMPARATOR

ART only arm

Intervention Type: DRUG

ART (efavirenz-based) only (+ pyridoxine 50mg) given within 2 weeks after enrolment

Interventions

Experimental: Empiric TB treatment

Initiation of 4 drug TB treatment (8 weeks of 4 drug, 16 weeks of 2 drug therapy) followed by ART (efavirenz-based) within 2 weeks

Intervention Type: DRUG

ART only arm

ART (efavirenz-based) only (+ pyridoxine 50mg) given within 2 weeks after enrolment

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Aged > 18 years old
• HIV-1 positive
• Eligible for antiretroviral treatment with CD4 T cell count < 50 cells/μl
• BMI < 18

Exclusion Criteria

• Patients with smear-positive pulmonary TB
• Patients who fulfill the diagnostic criteria for smear-negative pulmonary or extrapulmonary TB (http://www.who.int/tb/publications/2006/tbhiv_recommendations.pdf ).
• Previous TB treatment (history of TB medication for > 1 month
• History of using antiretroviral drugs
• Symptomatic known underlying liver disease or transaminases > 5x upper limit of normal
• Known or suspected drug resistance to more than one first-line TB drug according to WHO criteria but excluding HIV infection (e.g. household contacts of MDRTB patients)
• Pregnant or breast-feeding
• Patients with cryptococcal meningitis (CrAG positive with neurologic symptoms)
• Patients with other severe (opportunistic) disease such as disseminated KS, malignant lymphoma, toxoplasmosis who may not be able to tolerate anti-TB medication or require other specific therapy
• Patients with danger signs (respiratory rate > 30 per minute, heart rate > 120bpm, temperature > 39oC, and unable to ambulate)
• Taking other potentially life-saving medications (e.g. for other OIs, or immunosuppressants) that are incompatible with anti-TB chemotherapy or ART
• Unable to swallow TB medications
• Unable to follow-up at the clinic for regularly scheduled follow-up (e.g. too far from clinic)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

European and Developing Countries Clinical Trials Partnership (EDCTP)

OTHER_GOV

Sponsor Role: collaborator

Prof JMA Lange

OTHER

Sponsor Role: lead

Responsible Party

Prof JMA Lange

Executive Scientific Director AIGHD

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Frank Cobelens

Role: STUDY_DIRECTOR

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Yuka Manabe

Role: PRINCIPAL_INVESTIGATOR

Infectious Diseases Institute at Makerere University

Locations

Medical Research Unit, Albert Schweitzer Hospital

Lambaréné, , Gabon

Ministry of Health -Provincial Heatlh Directorate of the Sofala Province (Direcção Provincial de Saúde de Sofala DPSS)

Beira, , Mozambique

Infectious Diseases Institute University Makarere

Kampala, , Uganda

Countries

Gabon; Mozambique; Uganda

Related Links

http://amc.nl

Official Website of the sponsor

Other Identifiers

AIGHD_001

Identifier Type: -

Identifier Source: org_study_id